As used herein, the term GC/MS refers to a gas chromatograph (“GC”) interfaced to a mass spectrometer (“MS”). The term LC/MS refers to a liquid chromatograph (“LC”) interfaced to a mass spectrometer. The current practice in mass spectrometry is to have separate instruments for GC/MS and LC/MS operation. However, at least one manufacturer, Varian, Inc., manufactures a mass spectrometer that can be converted from an atmospheric pressure LC/MS to a vacuum ionization GC/MS by breaking the vacuum and interchanging ion sources.
This approach of converting an LS/MS to a GC/MS is time consuming, requires the breaking of a vacuum, and is only applicable on the specific Varian instrument. Waters and Bruker Corporations offer GC atmospheric pressure ionization mass spectrometer (“API-MS”) for instruments designed for LC/API-MS. In these instruments, the effluent from the GC is released into the AP ion source and ionized at AP using an electric discharge. Primarily protonated molecular ions are produced with most fragmentation being from even electron ions and thus are not directly capable of being computer matched to libraries of compounds in common use (e.g., the NIST library) which are generated from odd electron fragmentation using vacuum ionization methods. Thus, identification of unknowns by GC/APMS technology is difficult. However, APMS offers softer ionization with less fragmentation, which makes identification of the quasi molecular ion ([M+H]+, where M represents the molecular weight) easier.
Most currently available atmospheric pressure ionization mass spectrometers (“APIMS”) only interface to liquid introduction methods. U.S. Pat. No. 7,642,510 issued to McEwen (“McEwen”), the entirety of which is herein incorporated by reference, discloses an APIMS instrument that can ionize both liquid and gaseous effluents at atmospheric pressure. Typically, primary ions are formed at atmospheric pressure by initiation of a gaseous electrical discharge by an electric field or by electrospray ionization (“ESI”) as described in U.S. Pat. No. 6,297,499 issued to Fenn and U.S. Pat. No. 5,788,166 issued to Valaskovic et al., which are also herein incorporated by reference in their entireties. The primary ions in turn ionize the gas phase analyte molecules by either an ion-molecule process as occurs in atmospheric pressure chemical ionization (“APCI”), by a charge transfer process, or by entraining the analyte molecules in a charged droplet of solvent produced in the electrospray process by application of an electric field.
ESI is a method for producing gas phase ions from compounds in solution. In ESI, a liquid is typically forced from a small diameter tube at atmospheric pressure. A spray of fine droplets is generated when an electric potential is applied between the liquid emerging from the tube and a nearby electrode. Charges on the liquid surface cause instability such that droplets break from jets extending from the emerging liquid surface. Evaporation of the droplets leads to a state where the surface charge again becomes sufficiently high (near the Raleigh limit) to cause instability and further smaller droplets are formed. This process proceeds until free ions are generated by either the evaporation process described above or by field emission that occurs when the field strength in the small droplets is sufficiently high for field evaporation of ions to occur. Molecules more basic than the solvent being used in the ESI process are preferentially ionized as are compounds that concentrate at the surface of the droplet. Because ESI generates gas phase ions from a liquid, it is a good ionization method for interfacing LC to MS.
Because ESI is most sensitive and most suitable for basic and polar compounds, most LC/MS instrumentation incorporates an alternative atmospheric pressure ionization (“API”) technique called APCI. In APCI, a discharge is generated when a voltage causes electrical breakdown (formation of free electrons and ions) of the surrounding gas. The primary use of this atmospheric pressure ionization method has been as an ionization interface between liquid chromatography and mass spectrometry. This ionization method relies on evaporation of the liquid exiting the liquid chromatograph with subsequent gas phase ionization at atmospheric pressure in a corona discharge.
The primary ions produced in the corona discharge are from the most abundant species—typically nitrogen and oxygen from air or solvent molecules. Regardless of the initial population of ions produced in the corona discharge, diffusion controlled ion-molecule reactions result in a large steady state population of protonated solvent ions. These ions in turn ionize analyte molecules by proton transfer if the reaction is exothermic or by ion addition if the ion-molecule product is stable and infrequently by charge transfer reactions. While this technique tends to be more sensitive than ESI for low molecular weight and less polar compounds, it nevertheless is not sensitive for highly volatile compounds and those less basic than the LC solvent. Thus, neither APCI nor ESI are good ionization methods for a large class of volatile and less polar compounds.
For this reason, other ionization methods, such as photoionization have been applied to LC/MS to more effectively reach a subset of this class of compounds. Photoionization at atmospheric pressure uses an ultraviolet (“UV”) source for ionization of gas phase molecules. Typically, a plasma-induced discharge lamp that produces ultraviolet radiation in the range of 100-355 nanometers (nm) is used to generate ionization. Such a source, suitable for use with LC/MS, is available from Synagen Corporation of Tustin, Calif. McEwen (U.S. Pat. No. 7,642,510) discloses that volatile compounds introduced into the atmospheric pressure ion source of an API-MS instrument are more efficiently ionized when a solvent is not present.
Gas chromatographs may be interfaced with mass spectrometers with ion sources operating in a pressure regime near the vacuum of the mass spectrometer. The gas chromatograph is limited to volatile molecules but has higher resolving power for compound separation than LC. The gas chromatograph operates at atmospheric pressure and is interfaced to the mass spectrometry through capillary tubing or a so-called “jet separator”, both of which limit the volume of gas entering the vacuum ion source of the mass spectrometer. Gas chromatographs have also been interfaced to API sources as noted above.
So-called “multimode ion sources” are available which combine ESI and APCI for analysis of liquid effluents. Thus, in a single source design, liquid effluents can be ionized by APCI or ESI, but so far not also a gas effluent. No ion source is currently available that can ionize liquid and gaseous effluents from separation devices or solids, liquids, and gases by direct introduction and ionize volatile and nonvolatile high and low mass compounds with a single ionization source.